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OO
O
H
HO
Br
O
n-C
7
H
15
Br
+
n
n
or
n-C
8
H
17
Br
n = 1, 2
MOMO
OO
O
O
O
+
R
n
( )
5
O
228
R = n-C
8
H
17
, n = 1
229
R = n-C
7
H
15
, n = 2
2
MOMO
OH
OO
O
O
( )
5
R
226
and
227
n
O
230
R = n-C
8
H
17
, n = 1
231
R = n-C
7
H
15
, n = 2
Scheme 10-39. Synthesis of mimics 226 and 227 by Yao et al.
enantiopure diastereoisomers 232a-d became the synthetic targets and R- and S-
2,3-O-isopropylidene-glyceraldehyde were used as the chiral building blocks.
From S-2,3-O-isopropylidene-glyceraldehyde diol, 233 and iodide 234b were
derived, whereas diol 235 and iodide 236b were obtained in a similar way from
R-2,3-O-isopropylidene-glyceraldehyde. The combination of two nucleophiles
233 and 235 and the two alkylating agents 234b and 236b would then give four
linear esters, which after four-step conversions including a key aldol reaction,
afforded 232a-d, respectively. An example for the synthesis of 232c is illustrated
in Scheme 10-40. (Compounds 232a-d are numbered according to their parent bis-
THF acetogenin for easier comparison).
96,97
The cytotoxic results of mimics 232a-d toward some caner cells are shown in
Table 10-4. As can be seen, maintenance of the two free hydroxy groups originally
flanking bis-THF rings of acetogenin proved to be rewarding, and these mimics
TABLE 10-3. Cytotoxicity of Mimics 226 and 227 toward HL-60 and K562 Cells
IG %
HL-60
K562
cocn (mM)
100
10
1
100
10
1
cmp 226
100
50
0
31
18
0
cmp 227
100
65
21
55
25
22
Corossolone
68
29
0
53
16
2
(10RS)-Corossolin
63
56
5
10
2
0
Solamin
24
8
0
59
39
29
Bullatacin
73
7
0
53
39
27
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